PROJECT 006-TRANSLATIONAL RESEARCH AND INTERVENTIONAL ONCOLOGY PROGRAM PROJECT SUMMARY/ABSTRACT Paradigm-changing advances in biomedical research have made it possible to develop an increasing number of treatments precisely targeted to the unique biological, molecular and genetic features of an individual?s cancer. Translational Research and Interventional Oncology (TR) is a clinical research program that leverages Vanderbilt-Ingram Cancer Center (VICC) strengths in delivering cutting-edge precision medicine to patients with a broad diversity of malignancies. VICC was one of the lead academic institutions to implement genetic testing to identify ?actionable? tumor mutations and to use this information to inform clinical management, including enrollment in an extensive portfolio of genotype-driven clinical trials. TR leadership and membership were critical in advancing recent ?rationally-targeted? anti-cancer drugs and defining a paradigm shift in cancer therapy. The program leadership brings together clinical, translational, and basic investigators who share a common mission of translating basic and preclinical advances to the clinic. The program?s research strategy accelerates development of cancer therapeutics through intra- and inter-programmatic as well as trans-institutional collaborations. TR facilitates this culture of translation and collaboration by providing the fertile environment through programmatic activities and exchange that leads to dynamic interactions between investigators and trainees during the conduct of paradigm-shifting research that serves the VICC catchment area. To achieve strategic goals, the program members propose the following Specific Aims: 1) To translate advances in the understanding of molecular mechanisms of oncogenesis and tumor progression into novel therapeutic strategies; 2) To further develop genetically-directed early phase clinical trials, in part through the National Clinical Trials Network; 3)To understand mechanisms of resistance to genetically targeted therapy and develop novel strategies to prevent and overcome resistance; 4) To apply and enhance immune strategies in cancer and cellular therapy; and 5) To mentor and train the next generation of translational and clinical investigators. TR is co-led by Jeffrey Sosman, MD, Madan Jagasia, MBBS, MS, and Pierre Massion, MD. Their diverse backgrounds and areas of expertise are synergistic and will facilitate a collaborative ?team science? approach that it typically required to meet the goals of ambitious translational projects. The cancer focus, productivity and culture of collaboration within TR are evidenced by the scientific accomplishments as well as accrual of patients from the catchment area, region and nation to the TR interventional trials. There are 57 program members from 13 departments in the School of Medicine, with $2.0M in NCI funding and $3.2M in other peer reviewed cancer-related funding. Out of 655 publications, 17% are intra-programmatic and 28% are inter-programmatic. Members also have 240 collaborative publications with investigators at other institutions.